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Nucleotide Metabolism
Contents
Introduction
Bases, nucleosides and nucleotides
Metabolism
Processes involved in nucleotides biosynthesis
Biosynthesis of purine nucleotides
Biosynthesis of pyrimidine nucleotides
Catabolism of Purines
Catabolism of Pyrimidines
Conclusions
Introduction
Purines and pyrimidines are nitrogen-
containing heterocycles, cyclic
compounds whose rings contain both
carbon and other elements.
Nucleosides are derivatives of purines
and pyrimidines that have a sugar linked
to a ring nitrogen.
Nucleotides are nucleosides with a
phosphoryl group esterified to a hydroxyl
group of the sugar.
Bases, Nucleosides and Nucleotides
Bases, Nucleosides and Nucleotides
• Ingested nucleic acids and
nucleotides, which are dietarily
nonessential, are degraded in the
intestinal tract to mononucleotides,
which may be absorbed or converted
to purine and pyrimidine bases.
Metabolism
Metabolism is broadly divided into two categories:
1 . Catabolism : The degradative processes concerned with the breakdown of
complex molecules to simpler ones, with a concomitant release of energy.
2. Anabolism : The biosynthetic reactions involving the formation of complex
molecules from simple precursors
Process involved in nucleotides biosynthesis
These are, in order of decreasing importance
(1) Synthesis from amphibolic intermediates (synthesis de
novo).
(2) Phosphoribosylation of purines
(3) Phosphorylation of purine nucleosides.
Biosynthesis of purine nucleotides
Conversion of purines, their ribonucleosides, and their deoxyribonucleosides to mononucleotides
involves so called “salvage reaction.
Liver is the major site for purine nucleotide synthesis.
Erythrocytes, polymorphonuclear leukocytes and brain cannot produce purines.
Folic acid is essential for the synthesis of purine nucleotides. Folic (methotrexate) are employed
to control cancer.
Biosynthesis Of Pyrimidine Nucleotides
The catalyst for the initial reaction is cytosolic carbamoyl phosphate synthase
II, a different enzyme from the mitochondrial carbamoyl phosphate synthase I
of urea synthesis .
Compartmentation thus provides two independent pools of carbamoyl
phosphate. PRPP, an early participant in purine nucleotide synthesis, is a
much later participant in pyrimidine biosynthesis.
Mammalian cells reutilize few free pyrimidines, “salvage reactions” convert
the ribonucleosides uridine and cytidine and the deoxyribonucleosides
thymidine and deoxycytidine to their respective nucleotides.
ATP dependent phosphoryltransferases (kinases) catalyze the phosphorylation
of the nucleoside diphosphates 2′-deoxycytidine, 2′-deoxyguanosine, and 2′-
deoxyadenosine to their corresponding nucleoside triphosphates.
In addition, orotate phosphoribosyltransferase, an enzyme of pyrimidine
nucleotide synthesis, salvages orotic acid by converting it to orotidine
monophosphate (OMP).
Antifolate drugs and glutamine analogs inhibit purine biosynthesis.
The biosynthetic pathway for pyrimidine
nucleotides
Catabolism of purines
Humans convert adenosine and
guanosine to uric acid.
Adenosine is first converted to
inosine by adenosine deaminase.
In mammals other than higher
primates, uricase converts uric acid
to the watersoluble product
allantoin.
Since humans lack uricase, the end
product of purine catabolism in
humans is uric acid.
Degradation of uric acid in animals other
than man
Catabolism of pyrimidines
Pyrimidine catabolism are highly water-soluble: CO2,
NH3, β-alanine, and β-aminoisobutyrate .
Excretion of β-aminoisobutyrate increases in leukemia
and severe x-ray radiation exposure due to increased
destruction of DNA.
Humans probably transaminate β-aminoisobutyrate to
methylmalonate semialdehyde, which then forms
succinyl-CoA .
Since the end products of pyrimidine catabolism are
highly water-soluble, pyrimidine overproduction results
in few clinical signs or symptoms.
Conclusions
Coordinated regulation of purine and pyrimidine nucleotide biosynthesis
ensures their presence in proportions appropriate for nucleic acid biosynthesis
and other metabolic needs.
Pyrimidine nucleotides are synthesized from the precursors aspartate,
glutamine and CO2, besides ribose 5-phosphate.
Pyrimidines are degraded to amino acids, nomely β alanine and β
aminoisobutyrote which are then metabolized